Study to assess the efficacy and safety of Orismilast in Psoriasis
Research type
Research Study
Full title
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 2b Dose-Ranging Study to Evaluate the Efficacy and Safety of Orismilast in Adults with Moderate-to-Severe Plaque-Type Psoriasis
IRAS ID
305546
Contact name
Charlotte Ørsted Pedersen
Contact email
Sponsor organisation
UNION therapeutics A/S
Eudract number
2021-003209-22
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 1 months, 17 days
Research summary
Research Summary
This study is being conducted by UNION therapeutics A/S (the Sponsor) for research purposes. The study drug, called Orismilast, is being investigated as a potential treatment for psoriasis, a condition where the body produces too many skin cells. Orismilast works by blocking an enzyme (a protein in the body) called PDE-4 (phosphodiesterase type 4). PDE-4 is involved in the inflammation (swelling) of the skin which can present as psoriasis.
Orismilast is an investigational medication; “investigational” means the medicine is not yet licensed to be available on prescription and is still being tested. However, this study has been approved by the MHRA and an ethics committee to make sure it is properly designed and ethically justifiable.
The purpose of this research study is to learn how well the study drug works and how safe the study drug is compared with a placebo, a ‘dummy’ drug with no active ingredients.
In this study, Orismilast or placebo will be taken twice a day for 16 weeks.
Summary of Results
Research Sponsor:
UNION therapeutics A/S
When and where was the study carried out?
The study started on 30 December 2021 and finished on 20 December 2022. It was carried out at 26 sites across Germany, Poland, the UK and the USA.
Why is this study important?
The study looked at people with the most common type of psoriasis, called plaque psoriasis. People with plaque psoriasis have red and scaly patches of skin (plaques) that are often itchy and can be painful. People with plaque psoriasis may also have joint problems such as arthritis.
Many people with psoriasis have a mild version of the disease, with just a few plaques. Those taking part in this study have several plaques covering large areas of their body, known as moderate-to-severe psoriasis. A doctor can use an established scoring system called the Psoriasis Area and Severity Index, or PASI for short, to decide how severe a person’s psoriasis is. This involves measuring the size of the affected area of skin and how red, thick and scaly the plaque is.
Although there is no cure for psoriasis, treatment can manage the symptoms of the disease. Most medications for moderate-to-severe plaque psoriasis are taken as an injection. More medications, especially convenient options in tablet form, are needed to treat people with moderate-to-severe psoriasis.
What did the researchers want to find out?
• how well a new tablet called orismilast worked in people with moderate-to-severe plaque psoriasis;
• what the best dose of orismilast would be; and
• what side effects people who took it would have.
Who participated in the study?
In total, 202 people with moderate-to-severe plaque psoriasis took part in the study. Of these, almost three out of four were male. Study participants were between 21 and 76 years old, with an average age of 44 years.
Only adults (at least 18 years of age) who had moderate-to-severe plaque psoriasis for at least 2 months were allowed to take part in the study.
Reasons people were not allowed to take part in the study included:
• their psoriasis did not cover enough body surface area to be classified as moderate or severe
• laboratory test results (such as blood tests) that were lower or higher than allowed
• other diseases or medical conditions that would interfere with the study
What treatments were studied?
Two treatments were studied: orismilast and placebo (both in tablet form).
A placebo is a tablet that looks just like the study medication but does not have any medicine in it.
Three different doses of orismilast tablets were tested: 20 mg, 30 mg and 40 mg. The orismilast and placebo tablets had to be taken two times a day.
People were assigned to one of the treatments by chance. None of the people taking part in the study or their study doctors knew whether they took orismilast or placebo tablets (all tablets looked the same).
The same treatment was given each day (morning and evening) for 16 weeks.
What happened during the study?
After the first day of the study, participants had phone visits after 1 and 2 weeks, then visited the clinic every 4 weeks, including a visit 4 weeks after treatment was stopped. At each study visit, the doctor would see if there were improvements in their psoriasis symptoms. The main way to see how well orismilast worked in improving psoriasis symptoms was with the PASI. This involved the doctor measuring the size of the affected area of skin and how red, thick and scaly the plaques were in each study participant. A higher PASI means worse psoriasis, and a reduction in PASI means an improvement. The doctor also looked for any side effects of the treatment. The participants filled out questionnaires about their symptoms and how they felt in their day-to-day life.
What did the study show?
Main results of the study
When looking at PASI, psoriasis was much improved in people who took orismilast tablets for 16 weeks compared with before they started taking treatment. The improvements were bigger in people taking orismilast tablets (up to 64%) than in those taking placebo tablets (17%).
Improvements in psoriasis happened early in the study and could be seen after just 4 weeks of treatment.
Additional results of the study
More study participants taking orismilast than placebo had improvements in their day to-day life and reported they felt improvements in their symptoms of psoriasis, such as itching, pain, redness and cracked skin measured with a tool called the Psoriasis Symptom Scale. Many patients taking orismilast also tended to report that they felt an improvement in their quality of life compared with those taking placebo.
What side effects were observed?
Side effects are unwanted medical ‘events’ that the doctor believes may be caused by the medication used in the study. More people taking orismilast tablets had side effects compared with those who took placebo tablets. The types of side effects seen with orismilast were similar to those seen with other medications that work in a similar way.
When looking at how many people stopped taking their study medication before the study had ended, it was similar between people taking placebo, orismilast 20 mg and orismilast 30 mg. The numbers were higher for people taking orismilast 40 mg. In those taking placebo, the main reason people gave for stopping was that they did not see an improvement in their psoriasis. For orismilast, the main reason for stopping study medication was side effects related to the stomach or gut.
Most common side effects
For people taking orismilast tablets, the side effects that affected more than 5 out of 100 people were stomach- or gut-related, such as nausea and diarrhea. Headache was also a common side effect.
Serious side effects
Two people had to go to hospital during the trial, but neither case was related to taking orismilast tablets.
How will the study help patients and researchers?
In this study, researchers found that people given orismilast 20 mg and 30 mg tablets had the best improvements in their psoriasis, with the fewest side effects.
These results will inform the Sponsor on how to move forward with investigating this new treatment to help people manage their psoriasis.
Where can I find more information about the study?
More information about this study can be found by accessing the following links:
https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C01%7Cgmcentral.rec%40hra.nhs.uk%7Ca4521d1b412e4f86387b08dbbe6c207b%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638313143832218186%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=ODSWC%2B9jevMv2T9sVDesXQxAQkkGvf2gUqproOoiAUk%3D&reserved=0 (use search term: NCT05190419
https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=05%7C01%7Cgmcentral.rec%40hra.nhs.uk%7Ca4521d1b412e4f86387b08dbbe6c207b%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638313143832218186%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=SMJlgSQKay0slhPJhuXXjEw20h%2FunF%2BLc%2FkrIb%2BOC%2BU%3D&reserved=0 (use search term: 2021-003209-22 Information about the sponsor can be found on the UNION therapeutics website: https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.uniontherapeutics.com%2F&data=05%7C01%7Cgmcentral.rec%40hra.nhs.uk%7Ca4521d1b412e4f86387b08dbbe6c207b%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638313143832218186%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=MVaByX5D5NUQE3vwhTYl4nYIa%2Brmo2530lBcm42RDXg%3D&reserved=0REC name
North West - Greater Manchester Central Research Ethics Committee
REC reference
21/NW/0342
Date of REC Opinion
27 Jan 2022
REC opinion
Further Information Favourable Opinion